Since initially becoming available in late December 2020, COVID-19 vaccinations have been administered on a worldwide basis. By April 2023, approximately 13.5 billion doses of the vaccine have been administered worldwide, with over 70% of the global population having received at least one dose to date.1 Although these vaccines are generally considered safe, a number of side effects have been linked to COVID-19 vaccines. Many of these side effects are associated with autoimmune manifestations and/or exacerbations, including immune thrombotic thrombocytopenia, autoimmune liver disease, Guillain-Barré syndrome, IgA nephropathy, rheumatoid arthritis, and systemic lupus erythematosus.2,3 Although ocular complications are rare, acute uveitis has recently been documented in literature as a potential sequela of COVID-19 vaccines.4
Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune condition characterized by bilateral granulomatous panuveitis. Proposed as a T cell–mediated reaction to viral infections or cutaneous injury, VKH typically manifests as a flulike prodrome followed by a uveitic stage that involves a thickened posterior choroid and serous retinal detachments. VKH is primarily treated with an aggressive course of corticosteroids with subsequent tapering.
The following discussion involves an interesting case of a middle-aged female who presented with new acute panuveitis four days after receiving a COVID-19 vaccination booster.
A 50-year-old healthy Asian female presented to clinic with blurry vision, floaters, and photopsia in both eyes (OU) that started 3 days previous. Her only ocular history was having LASIK surgery OU, and she denied any history of being diagnosed with uveitis or having uveitis symptoms. On day 1 of presentation, her best-corrected visual acuity (BCVA) was 20/25 in the right eye (OD) and 20/30 in the left eye (OS). Anterior chamber examination was notable for 1+ cell and flare in each eye (OU), and both eyes had 1+ vitreous cell with trace haze. Fundus exam revealed bilateral multifocal serous detachments and pigment epithelial detachments (PEDs) with creamy, deep lesions in the posterior pole of the macula. Macular ocular coherence tomography (OCT) demonstrated multifocal lobular serous detachments, PEDs, and thickened choroid OU (Figure 1).
Ultrawidefield autofluorescence imaging demonstrated hypoautofluorescence corresponding to the creamy-colored, subretinal multifocal lesions, and fluorescein angiography showed early punctate staining and late pooling in a multifocal fashion (Figure 2). She did not report any recent illnesses, pertinent family history, or systemic changes. At the time, she was started on prednisolone acetate 1% OU every 2 hours while a uveitis workup was initiated. The differential diagnosis was surmised to be Vogt-Koyanagi-Harada (VKH) disease or acute posterior multifocal placoid pigment epitheliopathy (APMPPE).5
On day 2, the patient returned emergently with significant worsening of best-corrected visual acuity to 20/50 OU. Exam revealed worsening findings in both eyes with new cystoid macular edema and extensive bacillary layer detachments seen on OCT (Figure 3). Anterior chamber examination showed improvement with rare cells and no flare while vitreous findings were unchanged. At this point, when she was asked again about any possible recent health changes, she recalled receiving a COVID-19 vaccine booster 4 days prior to her initial presentation, but she again denied any other systemic changes, such as rashes, poliosis, or headaches. Based on these clinical findings alongside negative infectious laboratory workup, the patient was thought to have VKH and was started on oral prednisone 60 mg daily while continuing topical steroids.
On day 8 the patient reported improvement, with BCVA now 20/30 OD and 20/40 OS. Exam findings improved, as did OCT scans, which showed regressing subretinal fluid, PEDs, and bacillary layer detachments (Figure 3). The uveitis workup was complete and unremarkable.
On day 14, the patient’s exam and BCVA continued to improve to 20/25 OD and 20/30 OS. Both eyes had complete resolution of anterior chamber and vitreous inflammation. Oral and topical steroid tapering was initiated. Three months after presentation, the patient was successfully weaned off all medications with BCVA restored to her baseline of 20/20 OU. Both eyes were quiet and appeared normal on exam, and OCT showed a profound normalization without any fluid, PEDs, or choroidal thickening (Figure 4). The patient has not had any recurrences since the initial presentation and has now been stable for over 1 year.
Post-vaccination uveitis has been a known phenomenon for some time, but has drawn more attention recently as new COVID-19 vaccines are developed and administered.4,6 Furthermore, both VKH and APMPPE have been described following COVID-19 infections and vaccinations.7,8 This patient’s presentation, exam findings, and timing of her vaccination appear to be a VKH-like phenomenon that occurred shortly after her COVID-19 vaccination.
Similar to VKH, APMPPE is an inflammatory chorioretinopathy that presents with common clinical manifestations, including blurry vision following a flu-like illness. Dilated fundus exam findings in APMPPE manifest as creamy placoid lesions in the posterior pole. While there are overlapping features between VKH and APMPPE, bacillary layer detachments are more specific to VKH, although APMPPE can also be associated but less frequently.9,10 In terms of prognosis, APMPPE is typically a self-limiting condition that resolves within weeks to months. Ultimately, it’s possible that both VKH and APMPPE are on a spectrum, with some cases, such as this one, displaying features of both diseases.
Systemic corticosteroids are the mainstay of therapy for VKH, as well as topical, periocular, or intraocular steroids depending on the scenario. Slow tapering of medications is recommended, and long-term maintenance immunotherapy is needed for recurrent and/or chronic cases.11,12 Conversely, APMPPE is typically a self-limiting condition with low risk of recurrence or chronicity that does not often need treatment. However, recent evidence does suggest that corticosteroid treatment should be initiated in APMPPE patients with acute presentations and/or foveal involvement, due to the potential of a worse visual prognosis.5,13,14
Similar to other autoimmune conditions, uveitis can lead to significant morbidities (such as irreversible vision loss) if not diagnosed correctly and treated early on in the disease course. It is important to remain vigilant and take a thorough medical history, including asking about recent illnesses and vaccinations. It is not that uncommon for patients to inadvertently withhold valuable information during the first clinical encounter or two, so one should continue to inquire about possible uveitis etiologies at future encounters. Furthermore, the initial presentation of VKH has been reported in ages 3 to 89, but typically presents in the fourth decade of life (ages 30 to 39). In our patient’s case, her presentation at age 50 is less common and should be considered in reaching the diagnosis.
In our case, with close monitoring and prompt treatment early in the presumed VKH disease course, our patient had a rapid and complete recovery of her visual acuity and disease course. Timely recognition, treatment, and close monitoring of patients with uveitis, including VKH and APMPPE, are needed in order to achieve the best possible outcome. With the ever changing developments of the COVID-19 pandemic, the treating physician should be cognizant of the possible link to uveitis after COVID infection or vaccination. NRP
- Mathieu E, Ritchie H, Rodés-Guirao L, et al. Coronavirus (COVID-19) vaccinations. Our World in Data. Accessed February 17, 2023. https://ourworldindata.org/covid-vaccinations
- Chen Y, Xu Z, Wang P, et al. New-onset autoimmune phenomena post-COVID-19 vaccination. Immunology. 2022;165(4):386-401. doi:10.1111/imm.13443
- Ehrenfeld M, Tincani A, Andreoli L, et al. Covid-19 and autoimmunity. Autoimmun Rev. 2020;19(8):102597. doi:10.1016/j.autrev.2020.102597
- Cheng JY, Margo CE. Ocular adverse events following vaccination: overview and update. Surv Ophthalmol. 2022;67(2):293-306. doi:10.1016/j.survophthal.2021.04.001
- Oliveira MA, Simão J, Martins A, Farinha C. Management of acute posterior multifocal placoid pigment epitheliopathy (APMPPE): insights from multimodal imaging with OCTA. Case Rep Ophthalmol Med. 2020;2020:7049168. doi:10.1155/2020/7049168
- Pichi F, Aljneibi S, Neri P, Hay S, Dackiw C, Ghazi NG. Association of ocular adverse events with inactivated COVID-19 vaccination in patients in Abu Dhabi. JAMA Ophthalmol. 2021;139(10):1131-1135. doi:10.1001/jamaophthalmol.2021.3477
- Yepez JB, Murati FA, Petitto M, et al. Vogt-Koyanagi-Harada disease following COVID-19 infection. Case Rep Ophthalmol. 2021;12(3):804-808. doi:10.1159/000518834
- Olguín-Manríquez F, Cernichiaro-Espinosa L, Olguín-Manríquez A, Manríquez-Arias R, Flores-Villalobos EO, Kawakami-Campos PA. Unilateral acute posterior multifocal placoid pigment epitheliopathy in a convalescent COVID-19 patient. Int J Retina Vitreous. 2021;7(1):41. doi:10.1186/s40942-021-00312-w
- Kitamura Y, Oshitari T, Kitahashi M, Baba T, Yamamoto S. Acute posterior multifocal placoid pigment epitheliopathy sharing characteristic OCT findings of Vogt-Koyanagi-Harada disease. Case Rep Ophthalmol Med. 2019;2019:1-6. doi:10.1155/2019/9217656
- Ramtohul P, Engelbert M, Malclès A, et al. Bacillary layer detachment: multimodal imaging and histologic evidence of a novel optical coherence tomography terminology: literature review and proposed theory. Retina. 2021;41(11):2193-2207. doi:10.1097/IAE.0000000000003217
- Stern EM, Nataneli N. Vogt-Koyanagi-Harada syndrome. In: StatPearls. Treasure Island (FL): StatPearls Publishing; January 2022. Accessed February 17, 2023. https://www.ncbi.nlm.nih.gov/books/NBK574571/
- Rubsamen PE, Gass JD. Vogt-Koyanagi-Harada syndrome. clinical course, therapy, and long-term visual outcome. Arch Ophthalmol. 1991;109(5):682-687. doi:10.1001/archopht.1991.01080050096037
- Testi I, Vermeirsch S, Pavesio C. Acute posterior multifocal placoid pigment epitheliopathy (APMPPE). J Ophthalmic Inflamm Infect. 2021;11(1):31. doi:10.1186/s12348-021-00263-1
- Pagliarini S, Piguet B, Ffytche TJ, Bird AC. Foveal involvement and lack of visual recovery in APMPPE associated with uncommon features. Eye (Lond). 1995;9(Pt 1):42-47. doi:10.1038/eye.1995.6